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Biomedical subjects

M Freund

Publications and source records attributed to M Freund.

At least 199 records · Page 11Linked to original sources

Results of parenchymal and angiographic magnetic resonance imaging and neuropsychological testing of children after stroke as neonates.

We describe the long-term follow up of infants after neonatal stroke of the middle cerebral artery (MCA). Stroke was diagnosed by CT scan in eight full-term neonates. Three dimensional (volume) magnetic resonance angiography (MRA) is a noninvasive technique that images the arterial vessels without contrast agents. All patients, aged from 1.5 to 8.4 years, were investigated by MRI and MRA and by neuropsychological tests. Cognitive development was investigated by intelligence tests, tests of visual perception, motor and language development. Out of the eight patients, seven had a retarded mental and motor development, and 50% of the children were treated for epilepsy. Seven patients had a spastic hemiparesis. Seven out of eight children showed major cognitive deficits. In all patients, MRI revealed clear parenchymal defects with variable distribution patterns. MRA studies showed abnormalities corresponding to the expected vascular distribution. Children with complications at delivery, with seizures, and an interruption of the main stem of MCA as demonstrated on MRA had the least favourable long-term follow up prognosis with severe cognitive delays.

Cerebral Arteries↗

Granulocyte colony-stimulating factor enhances the expression of CD62 on platelets in vivo.

The expression of CD41, CD42 and CD62 on platelets was determined in ten patients with and without G-CSF treatment. CD41 and CD42 is expressed in nearly 100% of the platelets without change after G-CSF treatment. The expression of CD62 on the platelets' surface is significantly enhanced by G-CSF indicating a depletion of the alpha-granules. No platelet aggregation was observed. The enhanced secretion of thrombocyte-specific proteins does not induce aggregation but may promote ADP-induced aggregation. Furthermore, the surface-bound and soluble CD62 binds specifically to macrophages and endothelial cells and is involved in the regulation of inflammatory processes. Thus indirect mechanisms may supplement direct effects of G-CSF after chemotherapy.

Adult↗

Fludarabine single-agent therapy for relapsed low-grade non-Hodgkin's lymphomas: a phase II study of the German Low-Grade Non-Hodgkin's Lymphoma Study Group.

In a phase II study, 45 patients with advanced low-grade non-Hodgkin's lymphomas (NHLs) who had failed on or had relapsed after first-line chemotherapy were treated with a 5-day regimen of fludarabine, 25 mg/m2/d, by a 30-minute infusion. All patients were pretreated and had received one to 11 preceding regimens (median, three regimens). Histologic subtypes included 17 centrocytic/centroblastic NHLs, three centrocytic NHLs, 23 lymphoplasmocytoid immunocytomas, and one case each of peripheral T-cell and lymphocytic lymphoma. From 38 presently evaluable patients, 12 (31%) cases responded (five [13%] complete and seven [18%] partial remissions). Treatment-associated toxicity was mild to moderate, with myelosuppression comprising the major side effect. From the 12 complete and partial response patients, seven are currently in unmaintained remission for more than 12 months. These data indicate a high activity of fludarabine in heavily pretreated patients with low-grade NHL. Further investigations are warranted to assess the most appropriate usage for this highly promising agent at earlier stages of low-grade NHL therapy.

Adult↗

A constant flux system using the 'magnetic cell separator' (MACS) for highly efficient T-cell depletion.

A method for highly efficient T-cell depletion using a 'Magnetic Cell Separator' (MACS) is described. T-lymphocytes were depleted from peripheral blood samples of 37 patients with chronic lymphocytic leukemia (CLL). The flow speed in the MACS column was adjusted by a syringe-driver allowing a constant flow speed of about 100 microliters/min. The mean content of T-cells after depletion was 0.17% (S.D. +/- 0.27). The effectiveness of depletion was calculated to a mean 93.7%. There was no correlation between the proportion of CD3-positive cells before and after depletion.

CD3 Complex↗

[Hemimegalencephaly. Therapy with hemispherectomy].

Hemimegalencephaly is associated with a poor clinical course characterized by intractable seizures and severe encephalopathy. We present a case report of a girl with hemimegalencephaly. At the age of 9 month hemispherectomy was undertaken to preserve function of the other hemisphere. MRI and histologic examinations showed characteristic dysplastic malformations. Follow-up and the complications are described.

Cerebral Angiography↗

Competitive adsorption of human immunoglobulin G and albumin: consequences for structure and reactivity of the adsorbed layer.

The affinity of polyclonal anti-IgG for human IgG adsorbed on silica surfaces was investigated by two complementary techniques, scanning angle reflectometry and 125I radiotracing. Special attention was paid to compare the reactivity of IgG adsorbed directly or by exchange with already adsorbed albumin. In particular it was shown that (i) in the first case (direct adsorption) the reaction between anti-IgG and adsorbed IgG was in the ratio 1:1 and (ii) in the second case (adsorption by exchange) there was no reaction.

Adsorption↗

Treatment of relapsed or refractory adult acute lymphocytic leukemia.

Sixty-six adult patients were treated for relapsing or refractory acute lymphocytic leukemia (ALL). The induction treatment consisted in a (1) first phase with vindesine 3 mg/m2 intravenously (IV) on days 1, 8, and 15; daunorubicin 45 mg/m2 IV on days 1, 8, and 15; erwinia-asparaginase 10,000 U/m2 IV on days 7, 8, 14, and 15; and prednisone 60 mg/m2 orally on days 1 to 21 and a (2) second phase with cytarabine 3000 mg/m2 as a 3-hour infusion two times a day on days 1 to 4 (in patients greater than 50 years of age we used 1000 mg/m2), and etoposide 100 mg/m2 IV on days 1 to 5. Side effects of induction Phase I were predominantly hematologic with subsequent infections. In Phase II, some patients additionally had gastrointestinal, cutaneous, ocular, and hepatic toxicity. Five patients died during Phase I and another died during Phase II. Five of these patients had T-cell ALL. Thirty-four (64%) of 54 patients in their first relapse had a complete remission (CR) with a median disease-free survival (DFS) of 2.9 months. The median overall survival (OAS) was 6.6 months. Seven of 12 patients with primary refractory disease, a second relapse, or relapse after bone marrow transplantation (BMT) had a CR. The CR rate and survival after first relapse was significantly better in patients with a preceding CR of more than 18 months compared with those with a shorter preceding remission. The leukocyte count was a second significant but not independent risk factor. There was a negative correlation between the leukocyte count and the duration of the preceding CR. The duration of the preceding CR was the major prognostic factor for survival in multivariate analysis. Twenty-two patients received BMT. None of nine patients with autologous BMT is alive and disease-free; 5 of 13 who underwent allogeneic BMT are. It was concluded that this treatment efficiently induced remission with tolerable toxicity. The remission duration should be improved by optimized consolidation treatment.

Adult↗

Effect of estradiol treatment on male mice synaptonemal complexes: difference of sensitivity between neonates and adults.

The effect of estrogen on pachytene spermatocytes was studied with the assistance of the synaptonemal complex analysis under electron microscopy. Male NMRI mice were injected with estradiol benzoate from birth onwards and allotted to different groups according to the dose administered: 1) three injections of either 12.5 micrograms or 25 micrograms or 50 micrograms on d0, d5 and d10; 2) single injections of 50 micrograms either on d0 or on d5 or on d10; 3) double injections of 50 micrograms on d0 and d5; and 4) daily injection at the dose of 0.5 micrograms/g BW from d0 to d27. Animals were sacrificed on day 28, 60 and 90. Adult male mice were treated daily with E2B (0.5 micrograms/g BW) for one (from d30 to d60) or two months (from d30 up to d90) to test the age-related sensitivity to estrogen. A number of different SC anomalies were observed at each harvest time. Among all the anomalies, pairing failure (asynapsis) was predominant followed in decreasing order of importance by SC breakage (fragmentation of SCs), and heterotelomeric associations resulting either in quadrivalent-like figures or in trivalents. In E2B treated neonates the frequency of SC anomalies, which was less than 2% in controls, varied from 3.6 to 27% of pachytene cells regardless of the harvest time. In E2B treated adult mice, the SC anomalies were rare (< 4%), but significantly different from controls in which the frequency of SC aberrations did not exceed 1% of pachytene cells. The prevalence of anomalies appeared to be independent of the TW decrease. Our observations suggest that estrogens act indirectly on SCs. Different mechanisms of action are discussed.

Age Factors↗

Effects of tumour necrosis factor alpha on bone marrow aspirates of patients with acute myelogenous leukemia determined by flow-cytometric cell-cycle analysis.

Tumour necrosis factor alpha (TNF alpha) exerts cytotoxic and antiproliferative effects on neoplastic cells. It has been used as a therapeutic agent for solid tumours and haematological malignancies. We report on the ex vivo determination of the effect of recombinant human rhuTNF alpha on bone marrow aspirates by a bromodeoxyuridine/propidium iodide method. Cell samples were drawn after 0.5, 2, 4, 6, 8, 10, 22, and 25 h from short-term suspension bone marrow cultures from patients with acute myelogenous leukemia (AML). Flow-cytometric cell-cycle analysis was performed after double DNA staining with propidium iodide and anti-BrdU antibodies. By this method the effect of rhuTNF alpha on cell proliferation can be evaluated after only 35 h. In about two-thirds of the bone marrow aspirates of AML an inhibiting effect on rhuTNF alpha can be demonstrated, developing to its full extent after 10 h.

Biopsy, Needle↗

The role of GM-CSF in infection.

GM-CSF is a hemopoietic growth factor with substantial effects on the proliferation of neutrophils, eosinophils and monocytes/macrophages. Its physiologic role in infection is still poorly understood. The gene for GM-CSF is constitutively transcribed in cells substantial for antiinfectious response. Various cells are activated and induced by TNF and IL-1 to synthesize GM-CSF. No systemic GM-CSF levels can be detected in patients with infection. It is likely that GM-CSF plays its physiological role in the immediate vicinity of the cells by which it is secreted. GM-CSF functionally activates neutrophils, monocytes/macrophages and eosinophils. It may augment T-cell proliferation and function. GM-CSF is effective in mice infected with Staphylococcus aureus or Salmonella typhimurium. Its effect in infectious disease in man should be explored.

Animals↗

Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on circulating platelets.

The effect on platelets of rhG-CSF was studied in 20 healthy volunteers with the thrombometer, a specially developed device which is described in detail. Additionally, conventional aggregation tests were performed. Low doses of rhG-CSF enhance functional platelet activity, as shown by significant acceleration of the occlusion of the thrombometer channel. Similar results were found in conventional aggregation tests utilizing collagen for induction. At G-CSF concentrations of 0.1 and 1.0 ng/ml the time to response was significantly accelerated and the maximum response was observed in a higher proportion of platelets. However, the second phase of aggregation induced by epinephrine was significantly inhibited by 1.0 ng/ml G-CSF. The activation of platelets may be beneficial in thrombocytopenia, but it may also increase platelet turnover and platelet loss. Further investigation is needed to clarify the mechanism by which G-CSF exerts its effects on platelets.

Adult↗